Adenosine A1 receptor-mediated modulation of dopamine D1 receptors in stably cotransfected fibroblast cells.
The antagonistic interactions between adenosine A1 and dopamine D1 receptors were studied in a mouse Ltk- cell line stably cotransfected with human adenosine A1 receptor and dopamine D1 receptor cDNAs. In membrane preparations, both the adenosine A1 receptor agonist N6-cyclopentyladenosine and the GTP analogue guanyl-5'-yl imidodiphospate induced a decrease in the proportion of dopamine D1 receptors in a high affinity state. In the cotransfected cells, the adenosine A1 agonist induced a concentration-dependent inhibition of dopamine-induced cAMP accumulation. Blockade of adenosine A1 receptor signal transduction with the adenosine A1 receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine or with pertussis toxin pretreatment increased both basal and dopamine-stimulated cAMP levels, indicating the existence of tonic adenosine A1 receptor activation. Pretreatment with pertussis toxin also counteracted the effects of low concentrations of the A1 agonist on D1 receptor-agonist binding. The results suggest that adenosine A1 receptors antagonistically modulate dopamine D1 receptors at the level of receptor binding and the generation of second messengers.
Ferré
S
S
Department of Neuroscience, Karolinska Institute, S-171 77 Stockholm, Sweden.
Torvinen
M
M
Antoniou
K
K
Irenius
E
E
Civelli
O
O
Arenas
E
E
Fredholm
B B
BB
Fuxe
K
K
D000818:Animals; D001552:Benzazepines / Q000378:metabolism; D001667:Binding, Competitive; D015152:Blotting, Northern; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D018076:DNA, Complementary; D004298:Dopamine / Q000378:metabolism; D018492:Dopamine Antagonists / Q000378:metabolism; D006801:Humans; D051379:Mice; D058915:Purinergic P1 Receptor Antagonists; D017447:Receptors, Dopamine D1 / Q000235:genetics / Q000378:metabolism*; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection; D014316:Tritium; D014970:Xanthines / Q000494:pharmacology
D001552:Benzazepines; D018076:DNA, Complementary; D018492:Dopamine Antagonists; D058915:Purinergic P1 Receptor Antagonists; D017447:Receptors, Dopamine D1; D018047:Receptors, Purinergic P1; D014970:Xanthines; D014316:Tritium; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000242:Cyclic AMP; D004298:Dopamine